Oxidized low-density lipoprotein (OxLDL)
Biochemistry
| Molecular mass | 2.5 mDa |
|---|---|
| Composition | 22.3% phospholipids 5.9% triglycerides 9.6% free cholesterol 42.2% cholesterol ester 22% protein, mainly Apolipoprotein B100 |
| Synthesis | liver |
Clinical significance
Atherosclerosis is characterized by a narrowing of arterial walls due to the excessive accumulation of lipids. Low-density lipoprotein (LDL) is the principal form of cholesterol that accumulates in atherosclerotic lesions or plaques; however, LDL must first be modified into an oxidized structure (oxLDL). It works as pro inflammatory, chemotactic factor for macrophages and immune reactive cells. This oxLDL forms complexes with β2-glycoprotein 1 (β2GPI) that lead to transformation of macrophages to lipid holding foam cells mediated by the so-called scavenger receptors. The process is amplified by the presence of antibodies against the oxLDL-β2GPI-complex via Fcγ-receptors.
An early resp. increased development of atherosclerosis in patients with certain systemic auto-immune diseases cannot completely be explained by conventional risk factors. Oxidative stress that leads to formation of oxLDL and subsequently to complex formation with β2GPI is often found in these patients. Also in many patients with type 2 diabetes mellitus, increased values for oxLDL-β2GPI-complexes are found.
Indication
Antibodies against oxLDL-β2GPI complexes may represent a serologic risk factor for arterial thromboses and atherosclerotic cardiovascular diseases in patients with systemic autoimmune diseases such as systemic Lupus Erythematosus (SLE), Anti-phospholipid Antibody Syndrome (APS) and Type 2 diabetes mellitus.
Literature
- Hasunuma Y et al. Involvement of β2-glycoprotein I and anticardiolipin antibodies in oxidatively modified low-density lipo-protein uptake by macrophages. Clin Exp lmmunol 107, 569, 1997.
- Kobayashi K et al. A specific ligand for β2-glycoprotein I mediates autoantibody-dependent uptake of oxidized low-density lipoprotein by macrophages. J Lipid Res 42, 697, 2001.
- Kobayashi K et al. Circulating oxidized LDL forms complexes with β2-glycoprotein I: implication as an atherogenic autoantigen. J Lipid Res 44, 716, 2003.
- Lopez LR et al. Anti-β2-glycoprotein l and antiphosphatidylserine antibodies are predictors of arterial thrombosis in patients with antiphospholipid syndrome. Am J Clin Pathol 121, 142, 2004.
- Lopez D et al. Oxdized low-density lipoprotein/β2-glycoprotein I complexes and autoantibodies to oxLig-I/β2-glycoprotein I in patients with systemic lupus erythematosus and antiphospholipid syndrome. Am J Clin Pathol 121, 426, 2004.
- Lopez D et al. Autoantibodies against β2-glycoprotein I complexed with a lipid ligand derived from oxidized low-density lipoprotein are associated with arterial thrombosis in antiphospholipid syndrome. Clin Dev Immunol 10, 203, 2003.
- Jiang LY, Jiang YH, Qi YZ, Shao LL, Yang CH. Integrated analysis of long noncoding RNA and mRNA profiling ox-LDL-induced endothelial dysfunction after atorvastatin administration. Medicine (Baltimore). Jun 97(22), 2018.
- Zhou J, Abid MD, Xiong Y, Chen Q, Chen J. ox-LDL downregulates eNOS activity via LOX-1-mediated endoplasmic reticulum stress. Int J Mol Med. Dec 32(6), 1442-50, 2013.